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MetabolismTom Ransom

Division of Endocrinology and Metabolism

October 19. 2017

Relationships with commercial interests:

Grants/research support: Research trials: Principal/Sub Investigator, CDHA, Endocrinology Research, Centre for Clinical

Research. Sanofi, Astra Zenica, BMS, Merck, Sepracor, Pfizer, Servier, Lilly, Abbott, GSK,

Novartis, Novo Nordisk

Speaker’s bureau/honoraria: Speaking honoraria: Sanofi, Astra Zenica, BMS, Merck, Sepracor, Pfizer, Servier, Lilly, Abbott,

GSK, Novartis, Novo Nordisk

Consulting fees: Advisory Boards: Merck & Co., Boehringer Ingelheim, AstraZeneca, Novo Nordisk, Valeant

Other:

Conflicts of Interest

Outline

• Define

• Basal metabolic rate/energy expenditure

• Hormones and Metabolism

• Discusion

Wiktionary, the free dictionary 5,369,740 entries with English definitions from over 3,650 languages

• metabolism

• Etymology

• From French métabolisme, from Ancient Greek μεταβολή (metabolḗ, “change”), from μετά (metá, “meta-”) + βάλλω (bállō, “I throw”).

• pronunciation[edit]

• IPA(key): /məˈtæbəlɪzəm/

• Noun

• metabolism (countable and uncountable, plural metabolisms)

• 1.(physiology) The complete set of chemical reactions that occur in living cells.

ATP is the currency

Kreb’s Cycle

Food is the Fuel

Bomb Calorimetry

Atwater numbers

• Think caloric density• 1 gram protein = 4 kcal

• 1 gram CHO = 4 kcal

• 1 gram fat = 9 kcal

• 1 gram EtOH = 7 kcal

• 3500 kcal = 1 pound

One calorie is the amount of energy required to raise one gram of water one degree Celsius at sea level

Which meal has more calories?

Diet Induced Thermogenesis

Effects of Exerciseon Metabolic Rate

• Exercise dramatically increases metabolic rate

• Rate remains elevated for extended period afterwards (excess post-exercise O2consumption)• Duration depends on intensity of exercise

• Long-term exercise may elevate resting metabolic rate (RMR)

Speakman JR, et al: Proc Nutr Soc 2003; 62(3):621-34.

15

Glycogen

Associated with lots of water

Carbohydrate Loading

Carbohydrate Depletion (dehydration)

Weight change during a triathlon

TABLE 1. Body weights (kg) and changes in body weight (kg) of triathletes competing in the 2000 South African Ironman triathlon*** P < 0.0001. From: Sharwood: Clin J Sport Med, Volume 12(6).November 2002.391-399

Hitting the Wall

40 seconds tops

Communication in the Body

• “Electrical” – Nervous System • “Signals” - Hormonal

Hormone

• Greek hormao (to arouse or excite)

• Substance that is secreted into the circulation by endocrine glands and acts as a chemical effector in other tissues• May stimulate or supress

Types of hormones

• Classically a hormone is secreted into the blood and acts on distant tissues, e.g. IGF-1 (insulin-like growth factor) produced from the liver

• Paracrine – act within the same tissue, e.g. testosterone stimulates spematogenesis in the adjacent seminiferous tubules.

• Autocrine – act within the same cell, e.g. prostaglandins from adipocytes influence adipocyte growth

• Those secreted from nerve endings, e.g. ADH (antidiuretic hormone)

Hormone structure

• Steroids – cortisol, estradiol

• Proteins - insulin

• Tyrosine (an amino acid) derivatives – thyroid hormones and catocholamines

Hormone structure• Steroids and thyroid hormones are fat soluble and

diffuse across cell membranes to bind intracellular receptors• In order to be “soluble” in blood they require carrier

proteins, i.e binding globulins

• Protein hormones and catacholamines are water soluble and require cell surface receptors and elicit their effects through second messangers• Most protein hormones have binding globulins as well

Hormone levels vary as a function of age

2

0 20 40 60 80

Age (years)

Testo

ste

rone (

mg/d

)

4

6

8

Morley JE, et al. Metabolism 1997

Seasonal variations of hormones

Monthly variations

Daily variations

Pulsatility over the day

Pulsatility from minute to minute

The Pituitary is the Master Gland

Who is this?

36

Sample feedback loop

Hyperprolactinemia

This woman presented with carpal tunnel syndrome

An elderly gentleman presents with confusion and weight loss

Simple Approach to Endocrinopathies

• If a hormone is lacking replace it

• If there is too much of a hormone suppress it chemically or surgically